Delirium and related toxic and metabolic encephalopathies are potentially treatable and reversible cognitive disorders that are common in geriatric patients with medical illness. The Institute of Medicine has cited its "high prevalence and tremendous associated morbidity and costs" and has celled for further research leading to knowledge of basic mechanisms and effective interventions. Such research must complement that on Alzheimer's disease and other irreversible dementias; maintaining the cognitive functioning of the elderly requires further knowledge about both metabolic and structural brain disease. What is currently known about delirium is derived almost entirely from symptoms observed in patients with acute medical illnesses, usually in the inpatient setting; little is known of its prevalence or symptomatology when it occurs as a complication of chronic illness. Accordingly, a priority in further research must be on reconsidering and validating approaches to diagnosis and case identification. We are proposing a program of research consisting of three studies designed to investigate delirium and related disorders in vulnerable patient populations. Study I will evaluate the presence of clinical features associated with delirium in chronically ill vs. health geriatric subjects with normal cognitive status or mild impairment; the relevant parameters will include measures of attention, of the electroencephalographic (EEG) background, and of fluctuations in both cognitive and EEG measures. The other studies will extend ongoing work to develop and validate methods for case identification that are based on measures of change within the individual rather than upon the observation of symptoms or deficits that emerge in the pathological state. We propose to use prediction intervals derived from repeated cognitive and EEG measures in healthy subjects as a metric for quantifying the magnitude of change within the individual and for defining significant change as a categorical event. Study IIA will refine and validate these methods through observation of the effects of administering the drug diphenhydramine to healthy elderly volunteers. Study IIB will assess the validity and clinical applicability of these methods in a more naturalistic study comparing the cognitive and EEG effects of centrally acting anticholinergic medications with those of other (centrally-inactive) medications in patients being treated for urological or gastrointestinal disorders.